SINCE BEING personally involved during the 1970s in some of the early research on the role of selenium in preventing breast cancer, I have come to regard selenium as my favorite nutrient. From this research, I began to realize that selenium is possibly the most powerful anticancer nutrient there is. I am certainly not alone in singing the praises of selenium. Dr. E. J.
Crary states, "Selenium is the most potent broad-spectrum anticarcinogenic agent
that has yet been discovered." (3)

Selenium is a recently recognized anticancer agent, so a re-view of the studies on the subject can serve as both the background and history of this important micronutrient. When selenium is added in trace amounts (1-4 ppm) to the diet of laboratory animals, it protects against a wide variety of carcinogens. There are many studies of large human populations that demonstrate the powerful anticancer benefits of this important essential trace mineral. There is also research indicating that selenium has potential as a chemotherapeutic agent to treat
cancer.

Animal Studies

In the late 1970s at the University of California in San Diego, Dr. Gerhard Schrauzer studied the relationship between selenium and breast cancer in female
C1H mice which have an inbred
cancer-causing virus. The newborn pups get the cancer virus from the mother in the process of nursing. In the females, mammary tumors develop spontaneously later in life with an incidence ranging from 80 percent to 100 percent.

In one experiment Dr. Schrauzer added 2 ppm of selenium in the form of selenite to the drinking water of half of the €31-1 test mice. After fifteen months, 82 percent of the untreated mice used as controls had developed mammary tumors. However, only 10 percent of the mice that received selenium supplementation developed tumors. (11)

This research alone makes a very powerful statement. Over a 70 percent reduction in breast cancer was realized with trace amounts of selenium added to the diet. For many years now, Dr. Schrauzer has been saying, and I thoroughly agree with him, that if women would take 200-300 mcg of selenium daily, the majority of breast cancers could be eliminated within a relatively short period of time.

When I worked with Dr. Schrauzer at UCSD, I was in charge of his mouse colony and assisted in studies of the value of selenium supplementation in preventing brain aging. This experience showed me how dietary deficiency of an important nutrient can cause cancer and how adequate levels can prevent cancer from developing. I am now convinced that selenium is one of the most valuable nutrients in combatting cancer and certain other degenerative diseases.

Because of the convincing research that supports selenium's effectiveness as a cancer-preventive agent, it is disappointing that its use is not promoted and its value not publicized by the government. The National Cancer Institute is currently conducting a large-scale study of the effects of selenium supplementation. Until this study is completed the FDA will take no official stance. Since one study often leads to another it could be ten, twenty, or more years until selenium is officially recommended as a cancer preventive nutrient.

Producing Maximum Protection

In another study with mice, Dr. Schrauzer was able to show that for maximum protective effect, selenium supplementation must be introduced as early in life as possible. This is because malignant
transformation may occur even at a very young age, and selenium exerts its protective effects only prior to this event. This study also showed that dietary selenium prevents and retards tumor development only as long as it is supplied in adequate amounts, because it is a non-accumulating trace nutrient. (13)

The same study (13) showed that midlife cessation of selenium supplementation resulted in a subsequent rapid increase in the number of tumors. Therefore, selenium supplementation must be maintained throughout the entire life span.

Another important study showed that Selenium's anti-carcinogenic activity is exerted during both the initiation and the promotion phases of carcinogenesis. This research demonstrated that supplementary selenium retards the reappearance of tumors in animals whose tumors had regressed following ovariectomy. The authors state, "The data suggest that selenium is not only effective in prevention but can also be used as an adjuvant che-motherapeutic agent." (6)

A 1979 review of the role of selenium in preventing cancer concluded that supplementary selenium can reduce the incidence of tumors resulting from the administration of a wide variety of carcinogens. (4)

Studies in Humans \

The scientific and medical literature is filled with studies that demonstrate selenium's anticancer effects in humans. This chapter will be able to review only some of the most significant studies.

In an epidemiological study Dr. Raymond Shamberger categorized the states and cities in the United States according to whether there was high, medium, or low selenium availability in the diet. He demonstrated an inverse association between selenium availability and age-adjusted mortality for all types of cancer. The more selenium available, the lower the levels of cancer. (14)

In a worldwide study Dr. Schrauzer analyzed the blood-bank data from seventeen countries around the world. He reported that areas with low levels of selenium in the diet had higher levels of leukemia and cancers of the breast, colon, rectum, prostate, ovary, and lung. (12) For example, he found that the blood levels of selenium in Japan, Taiwan, Thailand, the Philippines,
Puerto Rico, and Costa Rica were over three times as high as samples from the United States and European countries. The corresponding breast cancer mortality rates in Europe and the U.S. were from two to five times greater than in Asian and Latin American countries with higher selenium levels in the soil.

I A study of over ten thousand men and women evaluated ¦ prediagnostic serum selenium levels and the risk of cancer. Sub-¦jects with the lowest selenium levels had twice the risk of developing cancer as those with the highest levels. (15) A similar study from Finland showed that subjects with serum selenium less than 45 mcg/liter had three times the risk of developing cancer as subjects with serum selenium levels greater than 45 mcg/liter. (8)

Throughout twenty-four regions of China, age-adjusted cancer mortality showed a strong inverse correlation with selenium blood levels. These regions were grouped into low-, medium-, and high-selenium regions. The total age-adjusted cancer mortality was found to be three times higher in the low-selenium regions, and twice as high in the medium-selenium regions. (16)

A county-by-county analysis of cancer mortality rates throughout the United States strongly confirmed the inverse association between selenium availability and total cancer mortality in both men and women. (1) In a study of skin cancers, lower plasma selenium levels were associated with higher levels of basal cell and squamous cell carcinoma. (2)

A review published in 1986 reports that at least fifty-five published studies confirm selenium's cancer-protective effect. The epidemiologic studies showed that low blood levels of selenium correlate with increased incidence of almost all kinds of cancer.

Selenium and Chemotherapy

My interest in selenium led to my learning about the work done by Dr. Robert C. Donaldson, an oncologist at the Veterans Administration Hospital in Saint Louis, Missouri. Dr. Donaldson found that his cancer patients had very low blood selenium levels, which agreed with the scientific literature linking low levels of selenium with increased rates of cancer. Deciding to study this problem, he enlisted the help of Nutrition 21, a company that
produces standardized organically bound high-selenium yeast. Nutrition 21 agreed to supply him with selenium rich yeast for his cancer patients.

Unfortunately, Dr. Donaldson met an untimely, early death before he was able to publish any of his research results. However, both his secretary at the VA hospital and officials at Nutrition 21 were kind enough to send me copies of Dr. Donaldson's files and correspondence discussing the tumor regressions he was getting with his cancer patients.

Dr. Donaldson discovered that in most of his patients, normal doses of selenium did not produce much of an increase in the blood levels of selenium. In fact, very high oral doses of selenium were required to bring up the blood levels of selenium in his cancer patients. In a letter to Nutrition 21 dated May 11, 1979, he indicated, "We are now able, with nearly 100 percent regularity, to increase the blood levels by several fold by giving 1,000 to 2,000 micrograms of selenium daily and then dropping back to a maintenance dose."

In one case, a dosage level of 2,700 mcg/day for two months followed by six weeks of 5,000 mcg/day was required to bring up the selenium blood levels. However, it must be emphasized that selenium is a trace mineral and the doses Dr. Donaldson was using are potentially toxic. Dosages from 2,700 mcg to 5,000 mcg per day could produce symptoms of selenium toxictty-in a normal person.

One important aspect of Dr. Donaldson's work is the discovery that many cancer patients apparently don't absorb selenium well. Potentially toxic levels of oral selenium had to be administered in order to achieve normal blood selenium levels. When normal blood selenium levels were reached, Dr. Donald-son documented marked improvement in his patients and, in some cases, remission of advanced cancers.

Donaldson*s work raised some interesting questions that merit further investigation. He noted that occasional patients with relatively low levels of selenium (.223 ppm) experienced dramatic tumor regressions when supplemental selenium raised blood levels to normal. For other patients, however, tumor regression was not evident until the levels reached .40 ppm to .50 ppm, while still others required reaching blood levels of .80 ppm. It
would be valuable to know why some patients require such high blood levels of selenium to show improvement.

Mechanism of Action

Glutathione peroxidase is one of the most important antioxidant enzymes in our immune system. This important enzyme is selenium dependent, with each molecule of the enzyme containing four atoms of selenium. (7) This enzyme protects cell membranes and tissues against the destructive effects of hydroxyl (OH) free radicals, and its antioxidant and anticancer effects are very much dependent on selenium availability. (10)

Selenium and selenium-containing compounds can bind with heavy metals such as lead, mercury, and cadmium so they can be removed from the body. It has also been shown that exposure to even low levels of these toxic metals can cause a depletion of selenium and eliminate its potential anticancer effects. (9)

Current Status

Research in the past twenty years has drawn attention to the essential trace element selenium. As a result, we now know that selenium is one of the most powerful nutritional anticancer agents discovered. It should be recognized, accepted, and promoted as
a vital part of future programs of nutritional cancer prevention.

Dr. Donaldson's research also suggests that selenium may have a role to play as a chemotherapeutic agent in the treatment of cancer. More research is needed to determine how long tumor regressions will last, what the optimum blood levels of selenium

I are for cancer therapy, and how much selenium is needed to maintain the results. But whatever remains to be learned, selenium may well become one of the superstars in cancer prevention and treatment.

Toxicity

One study in China reported that a daily dose of 500 mcg of selenium over a period of several years is safe for healthy humans. (5) The higher dosage levels of selenium that appear to
be necessary to help cancer patients can be toxic. Dr. Schrauzer reports that dosages of 2,000 to 5,000 mcg per day will produce toxicity symptoms after several months. However, since the early symptoms of selenium toxicity such as nausea, weakness, and discoloration of the fingernails are hardly ever overlooked, high doses have not been reported to have caused any fatalities.

Dosage

Because oral doses of selenium have to be so large to be thera-peutically effective, it is imperative to perform regular assays of blood selenium levels in each individual patient. Four years ago I instituted the administration of a 1,000-mcg intramuscular injection of selenium every other day during a twenty-one-day period for cancer patients. This route bypasses the intestines and avoids the problem of varying levels of selenium uptake in different patients.

Outpatients take between 300 and 400 mcg of organic selenium orally each day as a nutritional supplement. Close medical supervision combined with regular laboratory assessment of blood selenium levels is necessary to prevent toxicity when selenium is used to treat cancer.